Oggi in Oncologia
Final Results From the Randomized Phase III ASCENT Clinical Trial in Metastatic Triple-Negative Breast Cancer and Association of Outcomes by Human Epidermal Growth Factor Receptor 2 and Trophoblast Cell Surface Antigen 2 Expression
Sacituzumab govitecan (SG), a first-in-class anti-trophoblast cell surface antigen 2 (Trop-2) antibody-drug conjugate, demonstrated superior efficacy over single-agent chemotherapy (treatment of physician’s choice [TPC]) in patients with metastatic triple-negative breast cancer (mTNBC) in the international, multicenter, phase III ASCENT study … (leggi tutto)
Bardia et al. riportano i risultati finali dello studio ASCENT che studia il sacituzumab govitecan (SG), l’anticorpo farmaco-coniugato (ADC) che ha come bersaglio l’antigene di superficie delle cellule del trofoblasto 2 (Trop-2) legato al paylod citotossico SN-38 attraverso un linker idrolisabile.
Il SG è stato confrontato con la chemioterapia a scelta del clinico (TPC), in pazienti con carcinoma mammario triplo negativo metastatico (mTNBC) già precedentemente trattate con almeno due linee chemioterapiche.
Nell’analisi finale sono stati considerati come endpoint la progressione libera da malattia (PFS), la sopravvivenza globale (OS), le risposte e la durata delle risposte nella popolazione Intent-to-treat. Inoltre, è stata effettuata un’analisi post-hoc nel sottogruppo di pazienti con diversa espressione di HER2 0, HER2 low ed espressione della Trop2.
In termini di efficacia SG ha migliorato la PFS, con una mediana di 4.8 mesi vs 1.7 mesi della TPC (HR 0.41 [95% CI, 0.33 – 0.52), che indica una riduzione del 59% del rischio di progressione della malattia o di morte a favore del SG. SG ha migliorato anche la sopravvivenza globale (OS), con una mediana pari a 11.8 mesi vs 6.9 mesi della TPC (HR 0.51 [95% CI, 0.42-0.63), con una riduzione del 49% del rischio di morte sempre a favore SG. In termini di attività il SG rispetto al TPC ha raggiunto il 31% di risposte globali (vs 4%; p<.0001), il 40% di beneficio clinico (vs 8%; p<.0001), una mediana di durata di risposte di 6.3 mesi (vs 3.6) e un tempo alla risposta di 1.5 mesi (vs 1.5).
L’analisi stratificata per sottogruppo, relativamente alla variabile di espressione di Trop-2, non ha evidenziato differenze significative di efficacia. L’efficacia del SG nei tumori a bassa espressione di Trop-2 potrebbe essere spiegata dall’effetto bystander della molecola, dall’alta affinità di legame e dall’elevato rapporto farmaco-anticorpo, che portano a un’efficacia dell’attività antitumorale anche con bassa espressione antigenica.
Gli autori riconoscono le limitazioni, tra cui la natura esplorativa delle analisi di sottogruppo, le dimensioni del campione, l’uso di tessuti d’archivio e la mancanza di analisi pre-specificate. Tuttavia, concludono che il SG abbia migliorato gli esiti rispetto alla TPC nel mTNBC pretrattato, confermando che il test immunoistochimico di Trop-2 non è imprescindibile per il trattamento con SG.
Per quanto riguarda la popolazione di pazienti di cui era nota l’immunoistochimica (IHC) per HER2 (78% del totale), il 71% dei pazienti è risultato essere HER2 IHC 0, mentre il 29% HER2-Low. Anche in questo caso, l’analisi di sottogruppo relativa a questa variabile non ha mostrato differenze statisticamente significative.
L’analisi del profilo di sicurezza aggiornata, peraltro, non ha rilevato difformità rispetto alle precedenti analisi, dimostrando un livello di tollerabilità a SG complessivamente accettabile.
I risultati finali dello studio ASCENT confermano le iniziali implicazioni cliniche in termini di miglioramenti significativi della sopravvivenza libera da progressione e della sopravvivenza globale con SG rispetto alle opzioni chemioterapiche standard nelle pazienti affette da carcinoma mammario triplo negativo metastatico. Il sacituzumab govitecan rappresenta il primo ADC entrato nella strategia terapeutica dei tumori TN in fase avanzata e che ha determinato una revisione dell’algoritmo terapeutico in questo setting di pazienti dalla difficile gestione. Sono in corso studi in cui il SG è sperimentato in fasi più precoci (I linea metastatica associato o meno a pembrolizumab sulla base della espressione del PDL1 e a confronto con chemioterapia standard); tali risultati saranno di estrema importanza per la definizione futura del miglior profilo terapeutico della malattia TN in fase avanzata.
In Europa
Nivolumab Plus Ipilimumab Demonstrates Long-Term Survival Benefit in Patients with Advanced HCC Who Were Sorafenib Intolerant or Refractory
May 28, 2024 – At a minimum follow-up of 60 months in the CheckMate 040 study, longest duration of follow-up reported for an immunotherapy combination in previously treated patients with advanced hepatocellular carcinoma (HCC), the arm A regimen of nivolumab plus ipilimumab continued to demonstrate clinically meaningful responses and long-term survival benefit in patients who were sorafenib intolerant or refractory … (leggi tutto)
Adding 24 Months of ADT Improves Metastasis-Free Survival in Patients with Prostate Cancer Treated with Postoperative Radiotherapy
May 27, 2024 – Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of androgen deprivation therapy (ADT) to radiotherapy in the RADICALS-HD study did not improve metastasis-free survival compared with no ADT, although it did delay the time to salvage ADT. Furthermore, compared with adding 6 months of ADT, adding 24 months of ADT … (leggi tutto)
FDA Grants Accelerated Approval to Tarlatamab-dlle for Extensive Stage Small Cell Lung Cancer
May 24, 2024 – On 16 May 2024, the Food and Drug Administration (FDA) granted accelerated approval to tarlatamab-dlle (Imdelltra, Amgen, Inc.) for extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. Efficacy was evaluated in 99 patients with relapsed/refractory ES-SCLC with disease progression following platinum-based chemotherapy enrolled in DeLLphi-301 (NCT05060016) … (leggi tutto)
Neoadjuvant Dabrafenib Plus Trametinib Has High Pathological Response Rates in Clinical Stage III Melanoma, But Low Rates of Recurrence-Free Survival
May 24, 2024 – Updated analysis of the phase II NeoCombi study shows low rates of recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) at 5 years with neoadjuvant dabrafenib plus trametinib in clinical stage III melanoma. These survival outcomes are similar to those achieved with adjuvant targeted therapy alone. There was a trend toward improved RFS and overall survival (OS) … (leggi tutto)
EMA Recommends Extension of Indications for Alectinib to Adjuvant Treatment of Resected ALK-positive NSCLC
May 23, 2024 – On 25 April 2024, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending a change to the terms of the marketing authorisation for the medicinal product alectinib (Alecensa). The marketing authorisation holder for this medicinal … (leggi tutto)
Perioperative Treatment with Nivolumab Results in Significantly Longer Event-Free Survival than Chemotherapy in Patients with Resectable NSCLC
May 22, 2024 – In the CheckMate 77T study, the addition of perioperative nivolumab to neoadjuvant chemotherapy resulted in significantly longer event-free survival (EFS) than perioperative placebo added to neoadjuvant chemotherapy in patients with resectable stage IIA to IIIB non-small cell lung cancer (NSCLC). The study team also observed that a higher percentage … (leggi tutto)
Dall’FDA
FDA Approval Sought for Use of TLX007-CDx in PSMA PET Imaging of Prostate Cancer
May 28, 2024 – A new drug application seeking the approval of TLX007-CDx for use in the preparation of prostate-specific membrane antigen (PSMA) PET imaging of prostate cancer has been submitted to the FDA, according to an announcement from Telix Pharmaceuticals.1 TLX007-CDx is a new and proprietary cold kit designed to enable the use of a PSMA imaging product with an extended distribution profile compared with … (leggi tutto)
FDA Grants Priority Review to Isatuximab Combo for Newly Diagnosed, Transplant-Ineligible Myeloma
May 27, 2024 – The FDA has granted priority review to the supplemental biologics license application (sBLA) seeking the approval of isatuximab-irfc (Sarclisa) in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) for the treatment of patients with newly diagnosed, transplant-ineligible multiple myeloma.1 … (leggi tutto)
FDA Advisory Committee Recommends Approval of Shield Blood Test for CRC Detection in Average-Risk Adults
May 24, 2024 – The FDA’s Medical Devices Advisory Committee has strongly recommended the approval of Guardant Health’s Shield blood test for colorectal cancer (CRC) screening in adults 45 years of age and older who are at average risk of developing this disease.1 The recommendation represents the committee’s consensus on the safety and efficacy of Shield in its proposed intended use, as well as the committee’s conclusion that … (leggi tutto)
FDA Roundup: May 24, 2024
May 24, 2024 – TToday, the U.S. Food and Drug Administration is providing an at-a-glance summary of news from around the agency: On Thursday, the FDA announced that Medline Industries, LP, a firm marketing and distributing plastic syringes made in China within the U.S., initiated a recall to stop using affected products which includes unauthorized plastic syringes made in China. Additionally, on Tuesday, the FDA announced that Jiangsu Shenli Medical Production … (leggi tutto)
FDA Grants Fast Track Designation to VCN-01 in Metastatic Pancreatic Cancer
May 23, 2024 – The FDA has granted fast track designation to VCN-01 in combination with gemcitabine and nab-paclitaxel (Abraxane) for the treatment of patients with metastatic pancreatic adenocarcinoma, according to a press release.1 Treatment with intravenous VCN-01 is being explored in the ongoing, multinational phase 2b VIRAGE trial (NCT05673811) in combination with standard-of-care … (leggi tutto)
FDA Roundup: May 21, 2024
May 21, 2024 – Today, the U.S. Food and Drug Administration is providing an at-a-glance summary of news from around the agency: Today, the FDA announced that registration is open for the two-day virtual public meeting, “FDA’s Fifth Online Controlled Substances SummitExternal Link Disclaimer.” The goal of this summit, hosted in partnership with the Reagan-Udall Foundation for the FDA, is to identify innovative solutions to reduce the illegal availability … (leggi tutto)
Dall’ASCO
Real-World Data Show No Survival Advantage With Dual Immunotherapy in Patients With Very Favorable–Risk Metastatic RCC
May 23, 2024 – Researchers used the International Metastatic Renal Cell Database Consortium (IMDC) to assess how patients with favorable-risk metastatic renal cell carcinoma (mRCC) responded to first-line systemic therapy over 33 months. Patients with very favorable–risk mRCC had significantly worse 2-year overall survival (OS) when treated with combination nivolumab/ipilimumab than with a VEGF inhibitor … (leggi tutto)
KEYNOTE-240 Data Suggest CTNNB1 Mutations Do Not Predict for Poor Responses to Pembrolizumab in HCC
May 23, 2024 – An exploratory analysis of KEYNOTE-240 found that the presence of CTNNB1 mutations did not predict for clinical outcomes with pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) in the second-line setting. However, detection of CTNNB1 mutations in plasma via circulating tumor DNA (ctDNA) is highly concordant with detection in tissue via whole-exome sequencing (WES) … (leggi tutto)
A Message From ASCO Daily News Editor Dr. Neeraj Agarwal
May 23, 2024 – Dear 2024 ASCO Annual Meeting Attendees: Welcome to ASCO Daily News, the official news publication of the American Society of Clinical Oncology (ASCO). With a commitment to excellence, we strive to deliver high-quality scientific and educational summaries of the latest cutting-edge data. Our publication features contributions from physicians, oncology providers, and investigators worldwide … (leggi tutto)
Recommending Treatment for Patients With Relapsed DLBCL After CAR T-Cell Therapy
May 23, 2024 – Allogeneic transplant remains a worthy goal for eligible patients with diffuse large B-cell lymphoma (DLBCL) who experience relapse in the post–CAR T-cell therapy setting; however, other treatments show promise in improving outcomes. Bispecific antibodies should be considered for patients who experience relapse after CAR T-cell therapy, as they have the most evidence in this population and avoid repeatedly targeting … (leggi tutto)
Oncology Care Informed by Geriatric and Frailty Assessment Can Lead to Better Outcomes. How Digital Health Technology Can Help Expand These Assessments
May 23, 2024 – Choosing treatment type and intensity based on frailty rather than age more effectively minimizes the risk of over- and undertreating older patients.
Compared with standard oncology care, oncology care informed by geriatric and frailty assessment reduces severe treatment toxicity, improves quality of life, and increases communication and satisfaction with care … (leggi tutto)
Leveraging Multidisciplinary Care for Locally Advanced NSCLC
May 22, 2024 – Treatment approaches for locally advanced non–small cell lung cancer (NSCLC) have evolved rapidly since the advent of immunotherapy, presenting providers with more options, but also more difficult decisions regarding treatment selection, combination, and sequencing. A Case-Based Panel Session at the 2024 ASCO Annual Meeting will provide a practical framework … (leggi tutto)
Pillole dall’AIFA
27 maggio 2024 – Esiti riunione Commissione Scientifica e Economica del Farmaco (CSE)
Leggi tutto
27 maggio 2024 – Regolamentazione e uso clinico degli apteni per patch test (aggiornamento)
Leggi tutto
27 maggio 2024 – Comunicazione AIFA su Barbesaclone 25 mg
Leggi tutto
27 maggio 2024 – Attivazione web e pubblicazione schede di monitoraggio – Registro LUMYKRAS
Leggi tutto
27 maggio 2024 – Comunicazione AIFA su Barbesaclone 100 mg
Leggi tutto
24 maggio 2024 – Aggiornamento “Diario di bordo sulla Trasparenza”
Leggi tutto
24 maggio 2024 – Rapporto del CCNCE sui 40 Comitati Etici Territoriali e Relazione di attività
Leggi tutto
23 maggio 2024 – Tabelle farmaci di classe A e H al 15/12/2023
Leggi tutto
23 maggio 2024 – AIFA pubblica l’elenco dei farmaci innovativi per singola indicazione (anno 2023)
Leggi tutto
23 maggio 2024 – La Commissione Europea adotta il primo Implementing Act sulla valutazione clinica congiunta di HTA dei medicinali – JCA
Leggi tutto
23 maggio 2024 – Triptorelina – AIFA incontra le società scientifiche
Leggi tutto
22 maggio 2024 – Nota Informativa Importante su GIAPREZA (angiotensina II)
Leggi tutto
Dedicato ai Soci
Opportunità di lavoro in Oncologia
Consulta le posizioni disponibili nella vetrina riservata ai Soci AIOM o scarica il modulo per richiedere la pubblicazione di annunci
Appuntamenti
NELL’AGENDA DISPONIBILE SUL SITO DELL’ASSOCIAZIONE TUTTE LE INFORMAZIONI SUGLI EVENTI AIOM NAZIONALI, REGIONALI e ALTRI APPUNTAMENTI PATROCINATI DA AIOM
